Trachoma is the world's leading cause of preventable blindness. Pilot studies have found that azithromycin, a new long acting antibiotic was as effective as long courses of topical antibiotic in treating trachoma. These findings suggest that community wide treatment with azithromycin might be a practical method for trachoma control. We have organized a program project that has 4 research projects, supported by 4 cores, taking a multidisciplinary collaborative approach with the overall goal of determining whether community wide treatment with azithromycin is effective in the control of blinding trachoma. Research teams in Egypt, Gambia and Tanzania will compare community wide treatment with oral azithromycin to the current standard treatment, topical tetracycline. The specific aims of the project include an assessment of the efficacy of oral azithromycin on the treatment of clinically active trachoma. In addition, we will determine the effect of this antibiotic on chlamydial infection and developing trachoma in the endemic villages. The possible role of nasal carriage in ocular reinfection will be determined. The use of gene typing will allow us to determine the distribution of genotypes of Chlamydia trachomatis within the villages at outset and then to study the distribution of strains as they are introduced into the azithromycin-treated population. The kinetics and specificity of antichlamydial antibody in tears will be determined after treatment with oral azithromycin, and when reinfection occurs during the subsequent two years. This study will provide information relative to community wide treatment approaches, and on mucosal immune responses to C. trachomatis, but most important, a successful outcome to the project means that effective trachoma control is achievable.